We shall determine the amino acid sequence of histidinol dehydrogenase of Salmonella typhimurium, and use this enzyme as the basis of a broad study of structure, function, and genetic relationships. Mutant enzymes will be created with altered catalytic properties; their structures will be analyzed, and the changes will be related to the changes in function. In particular, we shall study pairs of mutants which show interactions between subunits such that they correct each other's defect (complementation). By collaborating with a crystallography group we plan to facilitate the analysis of the three-dimensional structure of the enzymes, and so relate the genetics and primary structure to the folding of the protein chain. Analysis of the changes in other mutant proteins will be used to study various aspects of gene structure and function, including the specificity of carcinogens, frameshift mutations, intergene spacers, and insertion sequences.